DIRECT VASOCONSTRICTION AND ENDOTHELIUM-DEPENDENT VASODILATION - MECHANISMS OF ACETYLCHOLINE EFFECTS ON CORONARY FLOW AND ARTERIAL DIAMETER IN PATIENTS WITH NONSTENOTIC CORONARY-ARTERIES
DIRECT VASOCONSTRICTION AND ENDOTHELIUM-DEPENDENT VASODILATION - MECHANISMS OF ACETYLCHOLINE EFFECTS ON CORONARY FLOW AND ARTERIAL DIAMETER IN PATIENTS WITH NONSTENOTIC CORONARY-ARTERIES
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DOI：
10.1161/01.cir.79.5.1043
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发表时间：
1989-05-01
期刊：
影响因子：
37.8
通讯作者：
MARSHALL, JJ
中科院分区：
文献类型：
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作者：
HODGSON, JM;MARSHALL, JJ
最近在冠状动脉疾病患者中描述了内皮依赖性血管舒张剂对乙酰胆碱的反应。这些研究仅确定了大心外膜动脉的反应。我们的研究旨在确定乙酰胆碱对心外膜直径、冠状动脉流量和血管阻力的综合影响。患有非狭窄心外膜冠状动脉的患者 (n = 64) 接受了冠状动脉造影，同时使用 3F 亚选择性多普勒导管记录冠状动脉血流速度。在推注乙酰胆碱（100μg i.c.）之前和之后测量心外膜动脉横截面积（ECA）、速度、估计流量（速度乘以面积）和血管阻力。在罂粟碱（12-15 mg ic）（一种非内皮依赖性血管扩张剂）后进行了类似的测量。乙酰胆碱导致 ECA 减少 19.+-.3%，而罂粟碱则使 ECA 增加 9.+-.2%。乙酰胆碱后估计流量增加 69.+-.12%，罂粟碱后估计流量增加 147.+-.12%。两种药物后耐药性均下降（乙酰胆碱，-17.+-.13%；罂粟碱，-61.+-.2%）。除五名患者外，所有患者在接受乙酰胆碱治疗后，经血管阻力均下降。这些患者的心外膜动脉明显收缩（ECA 减少 40.+-.8%）。乙酰胆碱对 ECA 和抵抗力的影响被阿托品（1 mg i.c.）阻断。硝酸甘油（300μg，静脉注射）导致乙酰胆碱收缩（-11.2.+-.3.1%）的同一患者的心外膜扩张（7.5.+-.2.8%）。使用内皮源性舒张因子 (EDRF) 抑制剂亚甲蓝进行预处理，乙酰胆碱可增强心外膜动脉血管收缩（之前为 -25.+-.7%，之后为 -47.+-.11%，p < 0.01），并导致血管阻力显着增加（之前为 -24.+-.10，之后为 +79.+-.41，p < 0.05）。亚甲蓝对非 EDRF 依赖性血管扩张剂罂粟碱和硝酸甘油的反应没有影响。这些数据表明：1) 乙酰胆碱对心外膜动脉（收缩）和较小阻力血管（扩张）有不同的影响，2) 对乙酰胆碱的净反应取决于直接血管收缩和 EDRF 介导的血管舒张之间的相互作用，3) 准确评估乙酰胆碱对冠状动脉循环的影响需要确定冠状动脉流量和心外膜动脉直径。
An endothelium-dependent vasodilator response to acetylcholine has been described recently in patients with coronary artery disease. Those studies determined responses only of large epicardial arteries. Our study was designed to determine the integrated effects of acetylcholine on epicardial diameter, coronary flow, and vascular resistance. Patients (n = 64) with nonstenoatic epicardial coronaries underwent coronary angiography with simultaneous recording of coronary flow velocity using a 3F subselective Doppler catheter. Measurements of epicardial arterial cross-sectional area (ECA), velocity, estimated flow (velocity times area), and vascular resistance were made before and after bolus administration of acetylcholine (100 .mu.g i.c.). Similar measurements were made after papaverine (12-15 mg i.c.), a nonendothelium-dependent vasodilator. Acetylcholine resulted in a reduction of ECA of 19 .+-.3%, whereas papaverine increased ECA by 9.+-.2%. Estimated flow increased 69.+-.12% after acetylcholine and 147.+-.12% after papaverine. Resistance fell after both agents (acetylcholine, -17.+-.13%; papaverine, -61.+-.2%). Transvascular resistance fell after acetylcholine in all but five patients. These patients had dramatic epicardial artery constriction (40.+-.8% decrease in ECA). The effect of acetylcholine on bth ECA and resistance was blocked by atropine (1 mg i.c.). Nitroglycerin (300 .mu.g i.c.) resulted in epicardial dilatation (7.5.+-.2.8%) in the same patients in whom acetylcholine caused constriction (-11.2.+-.3.1%). Pretreatment with methylene blue, an inhibitor of endothelium-derived relaxing factor (EDRF), potentiated epicardial artery vasoconstriction with acetylcholine (-25 .+-. 7% before versus -47 .+-. 11% after, p < 0.01) and resulted in a marked increase in vascular resistance (-24.+-.10 before versus +79.+-.41 after p < 0.05). Methylene blue had no effect on the response to the non-EDRF-dependent vasodilators papaverine and nitroglycerin. These data suggest 1) acetylcholine has differing effects on the epicardial arteries (constriction) and the smaller resistance vessels (dilation), 2) the net response to acetylcholine depends on the interplay between direct vasoconstriction and EDRF-mediated vasodilation, and 3) accurate assessment of the effects of acetylcholine on the coronary circulation requires determination of both coronary flow and epicardial artery diameter.